Introduction
A global pandemic was declared on March 11, 2020, by the World Health Organization caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the world is still coping up to the challenges thrown by the virus since then.[ 1 ] Emergence of SARS-CoV-2 has added to the six coronavirus species belonging to the genus Alphacoronavirus (HCoV-229E and HCoV-NL63) and Betacoronavirus (HCoV-OC43, HCoV-HKU1, SARS-CoV, and Middle East respiratory syndrome coronavirus [MERS-CoV]) that were known to cause infection in humans.[ 2 , 3 ]
In addition to old age, and individuals with comorbidities; pregnant women their fetuses, and newborns also represent a high-risk population Vulnerable to Covid-19 disease.[ 4 ] Pregnancy is a vulnerable period, requiring more care and attention regarding both the mother and her fetus. Various physiologic and immunologic changes are known to occur during pregnancy such as alteration in hormonal level, edema of respiratory tract mucosa, reduced lung volume due to gravid uterus/elevated diaphragm, and T-cell immunity changes. These conditions may predispose pregnant women toward COVID-19 infection and may, in turn, lead to fetal and maternal complications.[ 5 ]
Studies in the past on influenza and other respiratory viruses have shown that risk of obstetrical complication in pregnant females is increased as compared to nonpregnant females.[ 6 ] Similarly, SARS-CoV-2 and MERS-CoV have been documented to be associated with severe maternal illness, maternal death, and spontaneous abortion.[ 7 ] There is a significantly higher risk of preeclampsia/eclampsia, giving birth to low birth weight (LBW) and small for gestational age infants in pregnant women presenting with pneumonia. However, there are still insufficient data particularly from India to evaluate the impact of COVID-19 during pregnancy, differences in clinical course, and the potential risks to the unborn child; therefore, the present study was done to know the severity of COVID-19 disease in pregnant and nonpregnant females of reproductive age group.[ 8 ]
Materials and Methods
The present prospective observational cohort study was conducted at a tertiary care center of northern India over a period of 6 months (January 2021–June 2021). This study was approved by the Institutional Ethics committee, and a waiver of informed consent was granted because the research involved minimal risk to the patients. Females of reproductive age group (15–44 years) who were admitted in COVID-19 isolation ward with reverse transcription–polymerase chain reaction (RT-PCR)-positive COVID-19 disease were included in the study and followed till discharge.[ 9 ] These females were further divided into pregnant and nonpregnant groups for comparison. Categorization of the patients into mild, moderate, and severe was done according to the Ministry of Health and Family Welfare (MOHFW) guidelines.[ 10 ]
Outcomes of pregnancy and neonatal health were recorded till the discharge of the patient. On the basis of gestational age, newborns were divided as preterm (before 37 weeks), early term (37 0/7 weeks of gestation through 38 6/7 weeks of gestation), full term (39 0/7 weeks of gestation through 40 6/7 weeks of gestation), late term (41 0/7 weeks of gestation through 41 6/7 weeks of gestation), and postterm (42 0/7 weeks of gestation and beyond).[ 11 ] Newborns were further divided into extremely LBW <1000 g, very LBW (VLBW) <1500 g, LBW 2500 g, normal birth weight (NBW) <4000 g, and high birth weight >4000 g.[ 12 ]
Statistical analysis
Statistical analyses were conducted with Excel. We showed continuous variables directly as a range and categorical variables as a number (%).
Results
A total of 60 females in the reproductive age group (16–44) who were COVID-19 RT-PCR positive and admitted in the hospital were included in the study, among which 25 were pregnant and 35 nonpregnant. Age-wise distribution is shown in Table 1 .
Table 1: Age-wise distribution of pregnant and nonpregnant females belonging to reproductive age group
Among the pregnant females, 96% were in their 3rd trimester and 4% in the 2nd trimester.
52% (13) of the pregnant females were asymptomatic, 44% (11) had mild, and 4% (1) had moderate COVID-19 disease. None of the females had developed severe disease. On the other hand, among the nonpregnant females, majority of them, i.e., 74.28% (26), had mild disease, 20% (7) developed moderate disease, while 2.86% 1 each had severe and asymptomatic illness, respectively, as shown in Table 2 .
Table 2: Severity of COVID-19 disease among pregnant and nonpregnant females of reproductive age group
Symptomatic females presented with fever as the most common presentation. 100% (12) of the pregnant and 88.24% of nonpregnant females had fever. Other symptoms presented were dry cough 33.34 (4), shortness of breath 25% (3), myalgia 8.34% (1), and diarrhea 8.34% (1) in the pregnant female group while nonpregnant females presented with shortness of breath 32.35% (11), dry cough 20.59 (7), pain in abdomen 8.82% (3), diarrhea 8.82% (3), myalgia 11.76%, rhinitis 11.76% (1), and chest pain 11.76% (1) [Figure 1 ].
Figure 1: Frequency of symptoms in pregnant and nonpregnant females
Some of the COVID-19-positive pregnant females had comorbidities or developed some obstetrical complications; their maternal and neonatal outcome is shown in Table 3 .
Table 3: Obstetrical and neonatal outcome in pregnant females with comorbidities and complications
In the present study, 40% (10) of females had cesarean section, 32% (8) had normal delivery, and 4% (1)had abortion (induced) whereas 24% (6) of females continued their pregnancy with healthy live fetus at the time of discharge. The neonatal status of the babies born is shown in Table 4 .
Table 4: Neonatal status of the babies delivered by COVID-19-positive females
Discussion
The immunocompromised status of a pregnant female although not profound may predispose them to a more rapidly deteriorating clinical course. The present study aimed to determine the effect of COVID-19 in pregnant females and compare it with nonpregnant females of the reproductive age group.
Ninety-six percent of the COVID-19-infected pregnant females were in the 3rd trimester and 4% in the 2nd trimester. Similar figures of more than 95% of pregnant women being in their third trimester were reported in a systematic review article.[ 13 ]
In our study, 52% of the pregnant females were asymptomatic, 44% had mild, and 4% had moderate COVID-19 disease while none of them had severe COVID-19. This was contrary to what was expected keeping in mind the physiological changes that occur in pregnancy.[ 14 , 15 ] Most of the studies have shown majority of pregnant females having mild symptoms.[ 15 , 16 ] When their counterpart nonpregnant female was compared, majority of them, i.e., 74.28% (26), had mild disease, 20% (7) developed moderate disease, while 2.86% (1) each had severe and asymptomatic illness. None of the pregnant females developed severe COVID-19 pneumonia or died. Most of the pregnant females with COVID-19 were asymptomatic and presented at the hospital for some other ailments or had history of contact. The explanations to this high rate of asymptomatic presentation in pregnant females with COVID-19 may be due to screening strategy adopted by the hospital and more vigilant testing in pregnancy. A systemic review and meta-analysis reported that one-third or two-third of the pregnant women manifest the COVID-19-related symptoms less often than in nonpregnant women of reproductive age.[ 16 ]
Symptomatic females presented with fever as the most common presentation. One hundred percent (12) of the pregnant and 88.24% of nonpregnant females had fever. Other symptoms presented were dry cough 33.34 (4), shortness of breath 25% (3), myalgia 8.34% (1)and diarrhea 8.34% (1) in the pregnant female group while nonpregnant females presented with shortness of breath 32.35% (11), dry cough 20.59 (7), pain in abdomen 8.82% (3), diarrhea 8.82% (3), myalgia 11.76% (1), rhinitis 11.76% (1), and chest pain 11.76% (1). The percentages of pregnant women reporting fever, muscle aches, chills, headache, and diarrhea were lower than those reported among nonpregnant women, suggesting that signs and symptoms of COVID-19 might differ between pregnant and nonpregnant women. Maternal clinical manifestations reported were fever (53%), cough (32%), fatigue/malaise (13%), myalgia (11%), sore throat (5%), and shortness of breath (8%).[ 17 ] Clinical characteristics were fever (138/235 [58.72%]), cough (111/235 [47.23%]), and sore throat (21/235 [8.93%]).[ 13 ]
Cesarean section (40%) was more than vaginal delivery (32%) in pregnant females with COVID-19, similar findings was shown by Islam et al. with (63.38%) cesarean section and (33.62%) vaginal delivery.[ 13 ] An umbrella review by Ciapponi et al . also depicted that cesarean section was the frequently reported outcome.[ 18 ] Our finding were further supported by several studies around the world.[ 3 , 16 , 19–21 ] The reason for the higher rate of cesarean section could be a more cautious approach taken by the gynecologists in COVID-infected females.
Preterm delivery (42.1%) was the most common outcome. Similar findings were also reported by various studies.[ 13 , 15 , 16 , 18 , 19 , 22 ] However, obstetric complication not related to COVID-19 was the major contributor toward this than the worsening of COVID-19 symptoms.
Ten of the pregnant females infected with SARS-CoV-2 had comorbidity/complication such as gestational diabetes, eclampsia, preeclampsia, rheumatic heart disease, anemia, hypothyroidism, contracted pelvis, and hepatitis C virus reactive. Thirty percent of them continued their pregnancy after testing COVID-19 negative and were discharged with live fetus. Lower segment cesarean section was also the most common delivery method among these comorbid females. Out of the 7 pregnant females infected by SARS-CoV-2, 4 preterm and 1 early-term birth were seen. Pregnant females with severe preeclampsia had intrauterine death (IUD).
Although 42.10% of the neonates were preterm, 63.16% had NBW as per Indian standard. However, 21.05% of neonates had LBW, 5.26% were VLBW, and 10.52% had IUD. Oncel et al . also reported 26.4% of preterm delivery and 12.8% of LBW infants in its multicentric study.[ 22 ] None of the newborns showed clinical signs of vertical transmission. Similar findings were seen by Di Mascio et al . However, a systemic review and meta-analysis has reported the possibility of SARS-CoV-2 vertical transmission in the third trimester.[ 21 , 23 ]
Conclusion
From this study, we can state that clinical course of COVID-19 disease does not vary much in pregnant and nonpregnant females of reproductive age group. Although pregnant females with comorbidities or obstetrical complications need more care. Cesarean section rates are quite high in pregnant females with COVID-19 disease. Preterm birth and LBW are also quite predominant in them. The major limitation of the study was the small scale of it. Regularly changing admission protocols and COVID-19 testing criteria by regulatory authorities and hospital can also affect the study. Therefore, a large-scale multicentric study on Indian population would have been ideal. However, very few studies have been published from India which compared the pregnant and nonpregnant females of reproductive age group. This preliminary study provides some insight on course of COVID-19 disease in Indian pregnant women.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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